Abstract Over 6.5 million women in the U.S. suffer from Stress Urinary Incontinence (SUI), and yet only 200,000 women (3%) seek surgical intervention. The need for general anesthesia, prolonged recovery time, fear of incisions, and concerns about treatment failures are just some of the reasons behind patient hesitation to seek SUI therapy. As a result, the remaining women afflicted with SUI use disposable absorbable products with an estimated cost of billions of dollars to cope with, but not cure, their symptoms. Recently, radiofrequency (RF) energy has been used for transurethral thermal shrinkage and micro-remodeling of the endopelvic fascia as a nonsurgical treatment for SUI. The main limitation of RF energy is its limited tissue penetration depth, and hence, the need to invasively insert multiple RF needles into the submucosal tissue for thermal remodeling. We propose to develop a less invasive alternative procedure for treatment of SUI using deeply penetrating near-infrared laser energy in combination with applied contact cooling of the tissue surface, delivered through an endoscopic laser probe as a transvaginal approach to SUI treatment. The technique of delivering laser energy in combination with applied cooling has been exploited with great success in cosmetic dermatology applications. However, this technique has not yet been extended to other applications where targeting of deeper tissue structures is necessary. Our preliminary studies in a variety of soft tissues have demonstrated, both ex vivo and in vivo, that targeting and thermal alteration of subsurface tissues can be achieved using a laser in conjunction with contact cooling of the tissue surface, preserving 1-2 mm of the tissue surface from thermal necrosis. We hypothesize that for treatment of SUI, the vaginal mucosa can be completely preserved while the submucosal tissue is thermally remodeled, using an endoscopic laser probe with integrated cooling. We propose to design and test an endoscopic laser probe for minimally invasive transvaginal thermal treatment of female stress urinary incontinence. This project will involve: (1) experimental measurements and computer simulations of optical and thermal parameters of tissues; (2) design of an endoscopic transvaginal laser probe for use in treating female incontinence; (3) optimization of the laser and cooling treatment parameters; and (4) pre-clinical evaluation of the endoscopic laser probe for thermal tissue denaturation, shrinkage, and remodeling in a short-term, chronic porcine model.